Significance Cytomegalovirus (CMV) is a major cause of morbidity and mortality in AIDS patients and causes significant pulmonary pathology in HIV-infected individuals. Studies may define an in vivo system to test novel drugs and therapies aimed at preventing or limiting pulmonary damage in AIDS. Objectives The experimental design of this proposal will utilize rhesus macaques coinfected with rhesus cytomegalovirus (RhCMV) and simian immunodeficiency virus (SIV) to demonstrate in the lungs whether there is a relationship between (1) RhCMV expression and increased cytokine production by activated T cells, (2) cytokine production by T cells and increased SIV gene expression, (3) cytokine production by T cells and increased expression of adhesion molecules by endothelial cells, and (4) expression of adhesion molecules and increased SIV viral load. Results Seven juvenile macaques have been infected with RhCMV. All animals became viremic and developed antiviral antibodies. RhCMV disseminated throughout to multiple organs throughout the body, as determined by PCR detection of viral DNA. The spleen was the predominant site of viral gene expression, as determined by immunohistochemistry. The localization of cells within the spleen (in relation to the germinal centers) changed during the course of infection. These studies have established important virologic, immunologic, and molecular analysis of RhCMV infection in healthy juvenile macaques. In addition, 7 animals (seronegative for RhCMV) have been infected with RhCMV and SIV. Studies are in progress to compare the course of disease in these animals with animals infected with RhCMV or SIV alone. Future Directions Future work includes studies to investigate whether anamnestic immune responses can augment SIV replication and AIDS pathogenesis. This will be done by infecting RhCMV-seropositive animals with RhCMV and SIV. These studies are being conducted to determine whether activation of T cells responsive to RhCMV antigens increases SIV viral loads. KEYWORDS AIDS, HIV, cytomegalovirus